Alkamine esters of pyrrole sub



Patented Nov. 9, 1948 UNITED STATES PATENT OFFICE 2,453,674 ,y ALKAMINE ESTERS F 'PYRROLE SU -1 STITUTED AonY c Acmse Theodore F. Scholz, Plainfield, ,N. J., assignor to American Cyanamid Company, New York, N. Y., a corporation. of Maine a I No Drawingn, Application Novena or 14, 1946,

Serial No. 709,781

3 Claims. (01. 2607-313) This invention relates to alkamine esters of added with stirring while chilling the reaction pyrrole substituted acrylicacids. mixture, The addition of acid isstopped short of A number of alkyl' esters of pyrrole substituted neutralityand, the hydrochloride precipitate acrylic acids are known, but alkarn-ine esters have filtered off, washed with anhydrous: ether; and never been prepared as they cannot be obtained 5 vacuum dried. It has a melting point, of by ordinary methods. It is with these esters that 235.4-238.2 C. (corn). The compound, is soluble the present invention is concerned. in ethyl alcohol, chloroform and water, and in- The esters of the present invention may be used soluble in absolute ether. in various fields such as activation of rubber accel- The same compound is obtained when a correerators, local anaesthetics and the like. In gensponding amount of the dimethyl-1,2,4-trimethyleral the esters of the present invention are prepyrrole-5-carboxylate-Ii-acrylate is used instead pared by alcoholysis of the corresponding alkyl of the corresponding diethyl ester. The reaction esters using an alkali metal al'coholate as the proceeds in the same manner except that the ini catalyst. tial distillation temperature is that corresponding The alkyl esters which are the raw material to methyl alcohol instead of ethyl alcohol. from which the alkamine esters of the present Example 2 invention are prepared may be obtained by various known means, the best method being from The procedure f Example 1 is o w but h pyrrole aldehydes which are reacted with alkyl fi-diethylaminoethanol is replaced y a correacid malonates, such as ethyl acid malonate, in SD d amount of fly p p the presence of a base such as a piperidine The product obtained has substantially the same The alkamine esters of the present invention Properties as that f a p e are obtainable in the form of the free bases or in Example 3 the form of their salts, such as hydrochlorides. When used as local anaesthetics the latter form The Procedure of Example 1 18 followed the is preferred as it is in general more water soluble. lshiethylaminoethanhl is replaced l a cone The free bases, however, show greater effective- Spondmg amount of fi-dimethylammoethanolness as activators for rubber accelerators. The product Obtained has Substantially the Same The invention will be illustrated in greater Properties as that 9 Example detail in conjunction with the following specific Example 4 examples which are typical illustrations. The parts are by weight and temperatures are uncor- 1:116 procedure of Example 1 is followed but the meted unless other specified B-diethylaminoethanol is replaced by a corresponding amount of 'y-dlpropylaminopropanol. Example 1 The product obtained has substantially the same CHi-(fiC-OH=OHG0OGH;GH1N(O2H5): prop t s as that f a p In the foregoing examples the catalyst sodium (CzHsJzNCHaCHaOOCuK CH3 H0] is added to the dialkylamino alkanol where it, of course, reacts to produce the alcoholate. The CH3 40 addition of the sodium is in no sense critical. It 24 parts of diethy1 1,2,4 trimethy1pyn.o1e 5 may be added to the reaction mixture, or it may be carboxy1ate 3 acry1ate (prepared by reacting reacted either with the amino alcohol or with ethyLl, 2 4 trimethy1pyrro1e 5 ca1gboxy1ate 3 a1 ordinary ethyl alcohol to form an alcoholate and dehyde with ethyl acid malonate), are mixed with the ready formed elqohelete addhd to the reactmh 107 parts of fi-diethylaminoethanol to which a f The relatlve lhsenshflveness the small amount of metallic sodium has been added. actloh to the method of addition of the Sodhhh The mt is t heated at about the boiling alcoholate and the smoothness of the reaction 15 point of water for some time d the temperature in marked contrast to the ordinary characteristics then increased to about 150-160 0., ethyl alcohol of amino alcohols and their esters, which usually distilling over. When the vapor temperature are sensitive to oxidation in alkaline solution. No rises the pressure is lowered to 10 mm. and the reason is advanced here why the present reaction excess p-diethylaminoethanol distilled over. proceeds readily in spite of this normal tendency A residue is obtained which is extracted with to side reactions. ether, the extract washed with brine, dried and e a o t o alkali metal alcoholate P e e asolution of dry hydrogen chloride in ether slowly is not critical, but it should be in catalytic y f I 2,453,674

amounts, that is to say, amounts which are sufficient to vigorously catalyze the reaction but far below stoichiometric proportions. Good results are obtained with amounts of alcoholate of the order of mole per mole of the dicarbalkoxypyrrole. -This: hrQportiomis not. critical IJdJhe; term catalytic amounts will-he used in theclaims in its ordinary sense of small amounts far below stoichiometric proportions. Sodium can be replaced by potassium, but this presents no aduan .1

tage in the reaction and, therefore, does-not nomically warrant the higher cost of potassium. For this economic reason the sodiumalcohelxadzeis preferred as the catalyst. r

In many of the examples the hydrochlorides ls 1. Compounds selected from the group consisting of esters of 1,2,4-trimethylpyrrole-5-carboxy- 3-acrylic acid with dialkylamino alkanols and addition salts of the esters with strong acids.

2. Diw-diethylaminoethyl) -1,2,4-trimethylpyrrole fiy-carhogcylate -fi-acrylata barging the formula: i L 1 L:

3. A method of preparing bis(dialkylamino- Talley!) esters of 1,2,4-trimethylpyrrole-5-carboxylic acid-3-acrylic acid which comprise heating the-:dialkyl ester of the pyrrole carboxylic acrylic acid with the desired dialkylamino alkanol in the presence of-catalytic amountsof an: alkali metal alcoholate.

- No references cited? TrraoDoRE, 

